What is the recommended dosage of Keflex (Cephalexin) for treating cellulitis?

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Last updated: November 14, 2025View editorial policy

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Keflex Dosage for Cellulitis

For adults with typical non-purulent cellulitis, the recommended dose of Keflex (cephalexin) is 500 mg orally four times daily (every 6 hours) for 5 days. 1

Standard Dosing Regimen

  • Cephalexin 500 mg every 6 hours is the guideline-recommended dose for treating cellulitis in adults 2, 1
  • The FDA-approved adult dosage range is 1-4 grams daily in divided doses, with 250 mg every 6 hours being the usual dose, though 500 mg every 12 hours may be used for skin and skin structure infections 3
  • However, the IDSA specifically recommends the 500 mg four times daily regimen for cellulitis 1

Treatment Duration

  • A 5-day course is as effective as a 10-day course if clinical improvement has occurred by day 5 2, 1
  • Extend treatment beyond 5 days only if the infection has not improved 1
  • This shorter duration recommendation represents a significant departure from traditional 10-14 day courses and helps reduce unnecessary antibiotic exposure 2

When Cephalexin is Appropriate

  • Cephalexin is first-line for typical non-purulent cellulitis without systemic signs of severe infection 1
  • It provides excellent coverage against streptococci and methicillin-susceptible Staphylococcus aureus (MSSA), the primary pathogens in cellulitis 1
  • MRSA is an unusual cause of typical cellulitis, and β-lactam monotherapy with cephalexin is recommended in the absence of abscess, ulcer, or purulent drainage 2, 1

When to Consider MRSA Coverage Instead

Do not use cephalexin alone if any of these risk factors are present:

  • Penetrating trauma (especially injection drug use) 2, 1
  • Purulent drainage present 2, 1
  • Evidence of MRSA infection elsewhere 2, 1
  • Nasal colonization with MRSA 1

In these situations, add MRSA coverage with clindamycin, doxycycline, or trimethoprim-sulfamethoxazole to a β-lactam, or use clindamycin alone 2

Emerging Evidence on High-Dose Therapy

  • A 2023 pilot trial compared high-dose cephalexin 1000 mg four times daily to the standard 500 mg dose 4
  • Treatment failure occurred in only 3.2% with high-dose versus 12.9% with standard-dose 4
  • However, minor adverse events were more common with the high dose 4
  • This remains investigational and is not yet incorporated into guidelines, so standard 500 mg dosing remains appropriate 1

Critical Adjunctive Measures

  • Elevate the affected extremity to promote drainage of edema 1
  • Identify and treat predisposing conditions such as tinea pedis (toe web infections), venous insufficiency, lymphedema, or eczema 2, 1
  • Examine interdigital toe spaces in lower-extremity cellulitis, as treating fissuring or maceration reduces recurrence 1

Common Pitfalls to Avoid

  • Don't extend treatment to 10 days automatically - 5 days is sufficient if improvement occurs 1
  • Don't add MRSA coverage routinely for typical cellulitis without risk factors 1
  • Don't overlook underlying conditions that predispose to recurrent cellulitis 1
  • Don't forget that blood cultures are unnecessary for typical cases of cellulitis 2

When to Hospitalize

Consider inpatient management if:

  • Concern for deeper or necrotizing infection 1
  • Severely immunocompromised patient 1
  • Poor adherence to therapy expected 1
  • Outpatient treatment is failing 1
  • Systemic signs such as high fever, hypotension, or confusion 2

Penicillin Allergy Considerations

  • For patients with non-immediate penicillin allergy, cephalexin remains an option 1
  • For true immediate hypersensitivity reactions, use clindamycin 300-450 mg four times daily instead 5

References

Guideline

Cephalexin Dosing and Management for Cellulitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Antibiotic Recommendations for Cellulitis in Patients with Keflex Allergy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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